Data

NOTE: A total of 292 participants included in analysis after removing exclusion criteria.

Descriptives

Patient demographics

Characteristic Conventional (n=151) Non-conventional (n=141) Total (n=292) P-value
Age (y)at the time of result: Mean (SD) 65.37 (15.43) 68.73 (14.77) 66.99 (15.18) 0.06
Gender: N(%) 0.65
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Male 96 (63.6) 85 (60.3) 181 (61.99)
Female 55 (36.4) 56 (39.7) 111 (38.01)
Height (cm): Mean (SD) 171.19 (10.34) 170.45 (10.39) 170.83 (10.35) 0.55
Weight (kg)within the week prior to dose: Mean (SD) 88.14 (26.69) 98.29 (41.12) 93.04 (34.73) 0.01
BMI: Median (IQ range) 28.93 (24.23-33.71) 29.45 (24.97-39.68) 29.10 (24.43-35.06) 0.13
BMI: N(%) 0.12
Missing 10 (6.6) 4 (2.8) 14 (4.79)
<18.5 2 (1.3) 8 (5.7) 10 (3.42)
18.5 - 24.9 39 (25.8) 27 (19.1) 66 (22.60)
25 - 29.9 36 (23.8) 38 (27.0) 74 (25.34)
>=30 64 (42.4) 64 (45.4) 128 (43.84)
Estimated Glomerular filtration rate (mL/min)in the 24 h prior to the level: Mean (SD) 68.00 (30.61) 61.69 (28.59) 64.95 (29.77) 0.07
Estimated Glomerular filtration rate (mL/min)in the 24 h prior to the level: N(%) 0.001
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Stage 1: >=90 ml/min 60 (39.7) 42 (29.8) 102 (34.93)
Stage 2: 60-89 ml/min 40 (26.5) 27 (19.1) 67 (22.95)
Stage 3: 30-59 ml/min 24 (15.9) 51 (36.2) 75 (25.68)
Stag3 4/5: <30 ml/min 27 (17.9) 21 (14.9) 48 (16.44)
modified CG (mL/min): Mean (SD) 65.99 (37.18) 56.80 (37.60) 61.55 (37.60) 0.04
Inpatient length of stay: Median (IQ range) 12.00 (6.00-22.50) 14.00 (8.00-25.00) 13.00 (7.00-24.00) 0.13
Concurrent antiplatelet or anticoagulation treatment: N(%) 1.00
Missing 0 (0.0) 0 (0.0) 0 (0.00)
No 149 (98.7) 140 (99.3) 289 (98.97)
Yes 2 (1.3) 1 (0.7) 3 (1.03)
Clinical events after anticoagulation (choice=Death): N(%) 0.96
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 139 (92.1) 131 (92.9) 270 (92.47)
Checked 12 (7.9) 10 (7.1) 22 (7.53)
Clinical events after anticoagulation (choice=ACS): N(%) 0.48
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 151 (100.0) 140 (99.3) 291 (99.66)
Checked 0 (0.0) 1 (0.7) 1 (0.34)
Clinical events after anticoagulation (choice=VTE): N(%) 1.00
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 149 (98.7) 139 (98.6) 288 (98.63)
Checked 2 (1.3) 2 (1.4) 4 (1.37)
Clinical events after anticoagulation (choice=Ischaemic stroke in hospital): N(%) 0.23
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 151 (100.0) 139 (98.6) 290 (99.32)
Checked 0 (0.0) 2 (1.4) 2 (0.68)
Indication for enoxaparin(choose as many as apply) (choice=Pulmonary embolism): N(%) 0.22
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 61 (40.4) 68 (48.2) 129 (44.18)
Checked 90 (59.6) 73 (51.8) 163 (55.82)
Indication for enoxaparin(choose as many as apply) (choice=Deep vein thrombosis): N(%) 0.07
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 75 (49.7) 86 (61.0) 161 (55.14)
Checked 76 (50.3) 55 (39.0) 131 (44.86)
Indication for enoxaparin(choose as many as apply) (choice=Atrial fibrillation): N(%) 0.46
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 125 (82.8) 111 (78.7) 236 (80.82)
Checked 26 (17.2) 30 (21.3) 56 (19.18)
Indication for enoxaparin(choose as many as apply) (choice=Myocardial infarction): N(%) 0.36
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 150 (99.3) 138 (97.9) 288 (98.63)
Checked 1 (0.7) 3 (2.1) 4 (1.37)
Indication for enoxaparin(choose as many as apply) (choice=Metallic heart valve): N(%) 0.90
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Unchecked 145 (96.0) 134 (95.0) 279 (95.55)
Checked 6 (4.0) 7 (5.0) 13 (4.45)
Indication for enoxaparin (Other): N(%) 1.00
Missing 0 (0.0) 0 (0.0) 0 (0.00)
Yes 150 (99.3) 141 (100.0) 291 (99.66)
Other/Unknown 1 (0.7) 0 (0.0) 1 (0.34)
LMWH level: Mean (SD) 0.89 (0.35) 0.79 (0.32) 0.84 (0.34) 0.01
Major bleeding in hospital: N(%) 0.49
Missing 1 (0.7) 1 (0.7) 2 (0.68)
Yes 5 (3.3) 8 (5.7) 13 (4.45)
No 145 (96.0) 132 (93.6) 277 (94.86)
Enoxaparin dose used (mg): Mean (SD) 88.21 (25.29) 77.77 (32.60) 83.17 (29.47) 0.003
Enoxaparin dose (mg/kg): Mean (SD) 1.01 (0.11) 0.83 (0.30) 0.92 (0.24) <0.0001

eGFR

Enoxaparin dose used (mg): Mean (SD)
eGFR (mL/min) Conventional Non-conventional Overall P-value
<15 ml/min 81.3 (15.5) 78.8 (24.2) 80.4 (18.5) 0.8
15-29 ml/min 79.2 (25.4) 53.5 (21.8) 65.8 (26.6) 0.02
30-59 ml/min 85.8 (20.6) 69.6 (29.1) 74.8 (27.6) 0.02
60-89 ml/min 91.8 (22.2) 74.6 (24.1) 84.9 (24.3) 0.01
>=90 ml/min 90.3 (30.2) 97.0 (36.5) 93.1 (32.9) 0.2

Enoxaparin dose used (mg/kg): Mean (SD)
eGFR (mL/min) Conventional Non-conventional Overall P-value
<15 ml/min 0.986 (0.064) 0.702 (0.161) 0.887 (0.173) 0.002
15-29 ml/min 0.954 (0.038) 0.628 (0.218) 0.785 (0.228) <0.0001
30-59 ml/min 1.003 (0.101) 0.728 (0.196) 0.816 (0.214) <0.0001
60-89 ml/min 1.030 (0.157) 0.939 (0.363) 0.994 (0.262) 0.07
>=90 ml/min 1.010 (0.102) 0.986 (0.308) 1.000 (0.212) 0.6

eGFR (removed >10% dose)

Removed patients who had >10% dose in the non-conventional group.
Characteristic Non-conventional (n=141)
% diff conventional dose: N(%)
dose <10% 119 (84.4)
dose >10% 22 (15.6)


Enoxaparin dose used (mg): Mean (SD)
eGFR (mL/min) Conventional Non-conventional Overall P-value
<15 ml/min 81.3 (15.5) 78.8 (24.2) 80.4 (18.5) 0.8
15-29 ml/min 79.2 (25.4) 49.6 (17.5) 64.4 (26.1) 0.008
30-59 ml/min 85.8 (20.6) 69.7 (29.4) 74.9 (27.8) 0.02
60-89 ml/min 91.8 (22.2) 70.3 (22.5) 84.8 (24.3) 0.005
>=90 ml/min 90.3 (30.2) 102.2 (37.1) 94.3 (33.0) 0.05

Enoxaparin dose used (mg/kg): Mean (SD)
eGFR (mL/min) Conventional Non-conventional Overall P-value
<15 ml/min 0.986 (0.064) 0.702 (0.161) 0.887 (0.173) <0.0001
15-29 ml/min 0.954 (0.038) 0.586 (0.163) 0.770 (0.220) <0.0001
30-59 ml/min 1.003 (0.101) 0.718 (0.185) 0.810 (0.210) <0.0001
60-89 ml/min 1.030 (0.157) 0.748 (0.107) 0.939 (0.194) <0.0001
>=90 ml/min 1.010 (0.102) 0.845 (0.182) 0.955 (0.155) <0.0001

Descriptive plots

Subgroup analysis: Supratherapeutic LMWH levels (>1.0)

Table below is based on 76 patients with Anti-Xa levels >1.0.

Characteristic Conventional (n=50) Non-conventional (n=26) Total (n=76) P-value
Age (y)at the time of result: N(%) 0.48
Missing 0 (0.0) 0 (0.0) 0 (0.0)
<=65 years 21 (42.0) 8 (30.8) 29 (38.2)
>65 years 29 (58.0) 18 (69.2) 47 (61.8)
Age (y)at the time of result: N(%) 0.30
Missing 0 (0.0) 0 (0.0) 0 (0.0)
<=65 years 21 (42.0) 8 (30.8) 29 (38.2)
>65 to <=80 years 21 (42.0) 10 (38.5) 31 (40.8)
>80 years 8 (16.0) 8 (30.8) 16 (21.1)
BMI: N(%) 0.02
Missing 5 (10.0) 0 (0.0) 5 (6.6)
<30 16 (32.0) 15 (57.7) 31 (40.8)
30 - 40 22 (44.0) 4 (15.4) 26 (34.2)
>40 7 (14.0) 7 (26.9) 14 (18.4)
Estimated Glomerular filtration rate (mL/min)in the 24 h prior to the level: N(%) 0.31
Missing 0 (0.0) 0 (0.0) 0 (0.0)
>=30 mL/min 41 (82.0) 24 (92.3) 65 (85.5)
<30 mL/min 9 (18.0) 2 (7.7) 11 (14.5)
modified CG (mL/min): N(%) 0.88
Missing 0 (0.0) 0 (0.0) 0 (0.0)
<30 mL/min 8 (16.0) 4 (15.4) 12 (15.8)
30-50 mL/min 11 (22.0) 8 (30.8) 19 (25.0)
>50-80 mL/min 19 (38.0) 9 (34.6) 28 (36.8)
>80 mL/min 12 (24.0) 5 (19.2) 17 (22.4)

Model 1.1: LMWH ~ individualised dose, CrCl, age, weight

Model specifications - Outcome: LMWH level
- Covariates: individualised dose, modified CrCl, age, weight
- Model: Multiple linear regression
    Anti-Xa level ~ individualised dose + modified CrCl + age + weight

Bodyweight

Global test

model term df1 df2 F.ratio p.value
individualised_dose_used 1 287 8.228 0.004
modified_cg 1 287 0.019 0.9
age 1 287 0.613 0.4
weight 1 287 3.454 0.06

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.418 (-0.785, -0.051) 0.03
individualised_dose_usedNon-conventional -0.135 (-0.228, -0.043) 0.004
modified_cg 0.000 (-0.001, 0.002) 0.9
age 0.002 (-0.002, 0.005) 0.4
weight 0.001 (-0.000, 0.003) 0.06

Model diagnostics

Results

Overall

Contrast Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 0.873 (0.796, 0.958) 0.004

Adjusted means (95% CI)
individualised_dose_used response SE df lower.CL upper.CL
Conventional 0.833 0.027 287 0.782 0.888
Non-conventional 0.727 0.024 287 0.681 0.777

Modified CrCl

Contrast modified_cg Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 60 0.873 (0.796, 0.958) 0.004
(Non-conventional) / Conventional 61 0.873 (0.796, 0.958) 0.004

Bodyweight

Contrast weight Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 93 0.873 (0.796, 0.958) 0.004
(Non-conventional) / Conventional 94 0.873 (0.796, 0.958) 0.004

Age

Contrast age Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 66 0.873 (0.796, 0.958) 0.004
(Non-conventional) / Conventional 67 0.873 (0.796, 0.958) 0.004

BMI

Global test

model term df1 df2 F.ratio p.value
individualised_dose_used 1 273 7.675 0.006
modified_cg 1 273 0.019 0.9
age 1 273 0.299 0.6
bmi 1 273 4.836 0.03

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.409 (-0.810, -0.007) 0.05
individualised_dose_usedNon-conventional -0.134 (-0.230, -0.039) 0.006
modified_cg -0.000 (-0.002, 0.002) 0.9
age 0.001 (-0.003, 0.005) 0.6
bmi 0.005 (0.001, 0.009) 0.03

Model diagnostics

Results

Overall

Contrast Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 0.874 (0.795, 0.962) 0.006

Adjusted means (95% CI)
individualised_dose_used response SE df lower.CL upper.CL
Conventional 0.830 0.028 273 0.777 0.887
Non-conventional 0.726 0.025 273 0.679 0.776

Modified CrCl

Contrast modified_cg Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 60 0.874 (0.795, 0.962) 0.006
(Non-conventional) / Conventional 61 0.874 (0.795, 0.962) 0.006

BMI

Contrast bmi Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 29 0.874 (0.795, 0.962) 0.006
(Non-conventional) / Conventional 30 0.874 (0.795, 0.962) 0.006

Age

Contrast age Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 66 0.874 (0.795, 0.962) 0.006
(Non-conventional) / Conventional 67 0.874 (0.795, 0.962) 0.006

Model 1.2 (Sensitivity analysis): LMWH ~ individualised dose, CrCl, age, weight

Sensitivity analysis: Records with once-daily dosing excluded.

Model specifications - Outcome: LMWH level
- Covariates: individualised dose, modified CrCl, age, weight
- Model: Multiple linear regression
    Anti-Xa level ~ individualised dose + modified CrCl + age + weight

Bodyweight

Global test

model term df1 df2 F.ratio p.value
individualised_dose_used 1 227 10.472 0.001
modified_cg 1 227 0.760 0.4
age 1 227 0.489 0.5
weight 1 227 4.097 0.04

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.347 (-0.780, 0.086) 0.1
individualised_dose_usedNon-conventional -0.170 (-0.274, -0.067) 0.001
modified_cg -0.001 (-0.003, 0.001) 0.4
age 0.002 (-0.003, 0.006) 0.5
weight 0.002 (0.000, 0.003) 0.04

Model diagnostics

Results

Overall

Contrast Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 0.843 (0.760, 0.936) 0.001

Adjusted means (95% CI)
individualised_dose_used response SE df lower.CL upper.CL
Conventional 0.860 0.031 227 0.802 0.923
Non-conventional 0.725 0.027 227 0.674 0.781

Modified CrCl

Contrast modified_cg Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 60 0.843 (0.760, 0.936) 0.001
(Non-conventional) / Conventional 61 0.843 (0.760, 0.936) 0.001

Bodyweight

Contrast weight Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 93 0.843 (0.760, 0.936) 0.001
(Non-conventional) / Conventional 94 0.843 (0.760, 0.936) 0.001

Age

Contrast age Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 66 0.843 (0.760, 0.936) 0.001
(Non-conventional) / Conventional 67 0.843 (0.760, 0.936) 0.001

BMI

Global test

model term df1 df2 F.ratio p.value
individualised_dose_used 1 215 9.812 0.002
modified_cg 1 215 1.583 0.2
age 1 215 0.104 0.7
bmi 1 215 4.681 0.03

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.276 (-0.773, 0.220) 0.3
individualised_dose_usedNon-conventional -0.170 (-0.277, -0.064) 0.002
modified_cg -0.001 (-0.004, 0.001) 0.2
age 0.001 (-0.004, 0.006) 0.7
bmi 0.005 (0.000, 0.010) 0.03

Model diagnostics

Results

Overall

Contrast Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 0.843 (0.757, 0.939) 0.002

Adjusted means (95% CI)
individualised_dose_used response SE df lower.CL upper.CL
Conventional 0.857 0.032 215 0.796 0.922
Non-conventional 0.723 0.027 215 0.671 0.779

Modified CrCl

Contrast modified_cg Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 60 0.843 (0.757, 0.939) 0.002
(Non-conventional) / Conventional 61 0.843 (0.757, 0.939) 0.002

BMI

Contrast bmi Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 29 0.843 (0.757, 0.939) 0.002
(Non-conventional) / Conventional 30 0.843 (0.757, 0.939) 0.002

Age

Contrast age Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 66 0.843 (0.757, 0.939) 0.002
(Non-conventional) / Conventional 67 0.843 (0.757, 0.939) 0.002

Model 2.1: Risk of supratherapeutic LMWH levels

Model specifications - Outcome: LMWH level >1.0 (yes/no)
- Covariates: individualised dose, dosing frequency, modified CrCl, age, weight
- Model: Logistic regression
    Anti-Xa level ~ individualised dose + dosing frequency + modified CrCl + age + weight

In-range vs out-of-range

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 1.151 1 0.3
modified_cg 1.752 1 0.2
age 0.287 1 0.6
bmi 0.026 1 0.9

Model summary

Var Coefficients (95% CI) P-value
(Intercept) 0.360 (-1.742, 2.461) 0.7
individualised_dose_usedNon-conventional -0.275 (-0.777, 0.228) 0.3
modified_cg -0.006 (-0.015, 0.003) 0.2
age -0.006 (-0.027, 0.016) 0.6
bmi 0.002 (-0.021, 0.025) 0.9

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 0.76 (0.46, 1.26) 0.3

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 0.76 (0.46, 1.26) 0.3
(Non-conventional) / Conventional 61 0.76 (0.46, 1.26) 0.3

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 0.76 (0.46, 1.26) 0.3
(Non-conventional) / Conventional 30 0.76 (0.46, 1.26) 0.3

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 0.76 (0.46, 1.26) 0.3
(Non-conventional) / Conventional 67 0.76 (0.46, 1.26) 0.3

In-range vs below range

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 2.876 1 0.09
modified_cg 0.266 1 0.6
age 0.094 1 0.8
bmi 5.184 1 0.02

Model summary

Var Coefficients (95% CI) P-value
(Intercept) 0.047 (-3.277, 3.370) 1.0
individualised_dose_usedNon-conventional 0.660 (-0.115, 1.435) 0.10
modified_cg -0.004 (-0.017, 0.010) 0.6
age -0.005 (-0.039, 0.028) 0.8
bmi -0.048 (-0.093, -0.002) 0.04

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 1.94 (0.89, 4.20) 0.09

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 1.94 (0.89, 4.20) 0.09
(Non-conventional) / Conventional 61 1.94 (0.89, 4.20) 0.09

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 1.94 (0.89, 4.20) 0.09
(Non-conventional) / Conventional 30 1.94 (0.89, 4.20) 0.09

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 1.94 (0.89, 4.20) 0.09
(Non-conventional) / Conventional 67 1.94 (0.89, 4.20) 0.09

In-range vs above range

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 6.430 1 0.01
modified_cg 1.775 1 0.2
age 0.120 1 0.7
bmi 2.484 1 0.1

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.503 (-2.856, 1.850) 0.7
individualised_dose_usedNon-conventional -0.766 (-1.370, -0.162) 0.01
modified_cg -0.007 (-0.017, 0.003) 0.2
age -0.004 (-0.029, 0.020) 0.7
bmi 0.020 (-0.005, 0.045) 0.1

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 0.46 (0.25, 0.85) 0.01

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 0.46 (0.25, 0.85) 0.01
(Non-conventional) / Conventional 61 0.46 (0.25, 0.85) 0.01

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 0.46 (0.25, 0.85) 0.01
(Non-conventional) / Conventional 30 0.46 (0.25, 0.85) 0.01

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 0.46 (0.25, 0.85) 0.01
(Non-conventional) / Conventional 67 0.46 (0.25, 0.85) 0.01

In-range vs above range (>1.2)

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 0.689 1 0.4
modified_cg 0.014 1 0.9
age 1.788 1 0.2
bmi 0.658 1 0.4

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -3.641 (-6.932, -0.350) 0.03
individualised_dose_usedNon-conventional -0.318 (-1.073, 0.437) 0.4
modified_cg 0.001 (-0.013, 0.015) 0.9
age 0.022 (-0.011, 0.056) 0.2
bmi 0.014 (-0.019, 0.046) 0.4

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 0.73 (0.34, 1.55) 0.4

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 0.73 (0.34, 1.55) 0.4
(Non-conventional) / Conventional 61 0.73 (0.34, 1.55) 0.4

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 0.73 (0.34, 1.55) 0.4
(Non-conventional) / Conventional 30 0.73 (0.34, 1.55) 0.4

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 0.73 (0.34, 1.55) 0.4
(Non-conventional) / Conventional 67 0.73 (0.34, 1.55) 0.4

Model 2.2 (Sensitivity analysis): Risk of supratherapeutic LMWH levels

Sensitivity analysis: Records with once-daily dosing excluded.

Model specifications - Outcome: LMWH level >1.0 (yes/no)
- Covariates: individualised dose, dosing frequency, modified CrCl, age, weight
- Model: Logistic regression
    Anti-Xa level ~ individualised dose + dosing frequency + modified CrCl + age + weight

In-range vs out-of-range

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 1.067 1 0.3
modified_cg 1.631 1 0.2
age 0.162 1 0.7
bmi 0.377 1 0.5

Model summary

Var Coefficients (95% CI) P-value
(Intercept) 0.292 (-2.375, 2.959) 0.8
individualised_dose_usedNon-conventional -0.304 (-0.883, 0.275) 0.3
modified_cg -0.008 (-0.020, 0.004) 0.2
age -0.005 (-0.032, 0.021) 0.7
bmi 0.008 (-0.017, 0.032) 0.5

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 0.74 (0.41, 1.32) 0.3

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 0.74 (0.41, 1.32) 0.3
(Non-conventional) / Conventional 61 0.74 (0.41, 1.32) 0.3

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 0.74 (0.41, 1.32) 0.3
(Non-conventional) / Conventional 30 0.74 (0.41, 1.32) 0.3

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 0.74 (0.41, 1.32) 0.3
(Non-conventional) / Conventional 67 0.74 (0.41, 1.32) 0.3

In-range vs below range

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 4.132 1 0.04
modified_cg 0.176 1 0.7
age 0.004 1 1.0
bmi 4.421 1 0.04

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.925 (-5.035, 3.185) 0.7
individualised_dose_usedNon-conventional 0.974 (0.009, 1.940) 0.05
modified_cg 0.004 (-0.014, 0.021) 0.7
age -0.001 (-0.042, 0.039) 1.0
bmi -0.051 (-0.104, 0.002) 0.06

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 2.65 (1.01, 6.96) 0.05

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 2.65 (1.01, 6.96) 0.05
(Non-conventional) / Conventional 61 2.65 (1.01, 6.96) 0.05

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 2.65 (1.01, 6.96) 0.05
(Non-conventional) / Conventional 30 2.65 (1.01, 6.96) 0.05

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 2.65 (1.01, 6.96) 0.05
(Non-conventional) / Conventional 67 2.65 (1.01, 6.96) 0.05

In-range vs above range

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 6.600 1 0.01
modified_cg 3.390 1 0.07
age 0.089 1 0.8
bmi 3.985 1 0.05

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.211 (-3.232, 2.810) 0.9
individualised_dose_usedNon-conventional -0.889 (-1.587, -0.192) 0.01
modified_cg -0.013 (-0.027, 0.001) 0.07
age -0.005 (-0.035, 0.025) 0.8
bmi 0.028 (0.001, 0.055) 0.05

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 0.41 (0.20, 0.83) 0.01

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 0.41 (0.20, 0.83) 0.01
(Non-conventional) / Conventional 61 0.41 (0.20, 0.83) 0.01

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 0.41 (0.20, 0.83) 0.01
(Non-conventional) / Conventional 30 0.41 (0.20, 0.83) 0.01

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 0.41 (0.20, 0.83) 0.01
(Non-conventional) / Conventional 67 0.41 (0.20, 0.83) 0.01

In-range vs above range (>1.2)

Global test

LR Chisq Df Pr(>Chisq)
individualised_dose_used 1.008 1 0.3
modified_cg 0.522 1 0.5
age 1.774 1 0.2
bmi 1.212 1 0.3

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -3.579 (-7.617, 0.459) 0.08
individualised_dose_usedNon-conventional -0.434 (-1.289, 0.421) 0.3
modified_cg -0.007 (-0.025, 0.012) 0.5
age 0.027 (-0.013, 0.067) 0.2
bmi 0.020 (-0.015, 0.055) 0.3

Results

Overall

Contrast Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 0.65 (0.28, 1.52) 0.3

Modified CrCl

Contrast modified_cg Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 60 0.65 (0.28, 1.52) 0.3
(Non-conventional) / Conventional 61 0.65 (0.28, 1.52) 0.3

BMI

Contrast bmi Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 29 0.65 (0.28, 1.52) 0.3
(Non-conventional) / Conventional 30 0.65 (0.28, 1.52) 0.3

Age

Contrast age Odds ratios (95% CI) P-value
(Non-conventional) / Conventional 66 0.65 (0.28, 1.52) 0.3
(Non-conventional) / Conventional 67 0.65 (0.28, 1.52) 0.3

Model 3.1: LMWH levels ~ Enoxaparin dose (mg)

Overall

Model specifications
- Outcome: LMWH level
- Covariates: enoxaparin dose, modified CrCl, age, weight
- Model: Multiple linear regression (with non-linear terms for enoxaparin dose)
    Anti-Xa level ~ enoxaparin dose + modified CrCl + age + weight

Global test

model term df1 df2 F.ratio p.value
enox_dose 1 225 15.580 0.0001
modified_cg 1 225 7.111 0.008
age 1 225 1.547 0.2
weight 1 225 11.572 0.0008

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.644 (-1.100, -0.187) 0.006
ns(enox_dose, 3)1 0.845 (0.590, 1.100) <0.0001
ns(enox_dose, 3)2 1.874 (1.301, 2.447) <0.0001
ns(enox_dose, 3)3 1.207 (0.727, 1.688) <0.0001
modified_cg -0.002 (-0.004, -0.001) 0.008
age 0.003 (-0.001, 0.007) 0.2
weight -0.004 (-0.006, -0.002) 0.0008

Model diagnostics

Estimated marginal means

Enoxaparin dose used (mg) Estimated LMWH level SE df Lower 95% CI Upper 95% CI
25 0.38 0.05 225 0.30 0.48
60 0.66 0.03 225 0.60 0.72
80 0.82 0.03 225 0.77 0.87
100 0.95 0.04 225 0.88 1.03
200 1.70 0.37 225 1.11 2.61

Post-hoc comparisons

NOTE: Ratio of Geometric means for every 10 unit increase in Enoxaparin dose.

Contrast Ratio of Geometric means (95% CI) P-value
enox_dose90 / enox_dose80 1.084 (1.035, 1.134) 0.0006

By dosing strategy

Model specifications
- Outcome: LMWH level
- Covariates: enoxaparin dose, dosing strategy, modified CrCl, age, weight
- Model: Multiple linear regression (with non-linear terms for enoxaparin dose)
    Anti-Xa level ~ enoxaparin dose + dosing strategy + enoxaparin dose*dosing strategy+ modified CrCl + age + weight

Global test

model term df1 df2 F.ratio p.value
enox_dose 1 223 11.132 0.0010
individualised_dose_used 1 223 0.366 0.5
modified_cg 1 223 6.917 0.009
age 1 223 1.689 0.2
weight 1 223 10.024 0.002
(confounded) 1 223 1.223 0.3

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -0.586 (-1.084, -0.089) 0.02
ns(enox_dose, 3)1 0.794 (0.463, 1.124) <0.0001
ns(enox_dose, 3)2 1.720 (0.913, 2.527) <0.0001
ns(enox_dose, 3)3 1.105 (0.499, 1.710) 0.0004
individualised_dose_usedNon-conventional -0.095 (-0.401, 0.212) 0.5
modified_cg -0.002 (-0.004, -0.001) 0.009
age 0.003 (-0.001, 0.007) 0.2
weight -0.004 (-0.006, -0.001) 0.002
individualised_dose_usedNon-conventional:enox_dose 0.001 (-0.002, 0.005) 0.5

Model diagnostics

Estimated marginal means

Dosing strategy Enoxaparin dose used (mg) Estimated LMWH level SE df Lower 95% CI Upper 95% CI
Conventional 25 0.40 0.07 223 0.28 0.57
Non-conventional 25 0.37 0.05 223 0.29 0.48
Conventional 60 0.66 0.04 223 0.58 0.75
Non-conventional 60 0.65 0.03 223 0.59 0.72
Conventional 80 0.81 0.03 223 0.75 0.88
Non-conventional 80 0.82 0.04 223 0.75 0.89
Conventional 100 0.94 0.04 223 0.86 1.02
Non-conventional 100 0.97 0.06 223 0.87 1.09
Conventional 200 1.58 0.39 223 0.98 2.56
Non-conventional 200 1.85 0.46 223 1.14 3.01

Post-hoc comparisons

Contrast Enoxaparin dose used (mg) Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 25 0.94 (0.74, 1.18) 0.6
(Non-conventional) / Conventional 60 0.98 (0.85, 1.13) 0.8
(Non-conventional) / Conventional 80 1.01 (0.90, 1.12) 0.9
(Non-conventional) / Conventional 100 1.03 (0.92, 1.16) 0.6
(Non-conventional) / Conventional 200 1.17 (0.80, 1.71) 0.4

NOTE: Ratio of Geometric means for every 10 unit increase in Enoxaparin dose.

Contrast individualised_dose_used Ratio of Geometric means (95% CI) P-value
enox_dose90 / enox_dose80 Conventional 1.080 (1.028, 1.133) 0.002
enox_dose90 / enox_dose80 Non-conventional 1.093 (1.039, 1.150) 0.0006

Model 3.2: LMWH levels ~ Enoxaparin dose (mg/kg)

Overall

Model specifications
- Outcome: LMWH level
- Covariates: enoxaparin dose (mg/kg), modified CrCl, age
- Model: Multiple linear regression (with non-linear terms for enoxaparin dose)
    Anti-Xa level ~ enoxaparin dose + modified CrCl + age

Global test

model term df1 df2 F.ratio p.value
enox_dose_mgkg 1 226 10.788 0.001
modified_cg 1 226 2.708 0.1
age 1 226 0.246 0.6

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -1.014 (-1.553, -0.475) 0.0003
ns(enox_dose_mgkg, 3)1 0.716 (0.454, 0.978) <0.0001
ns(enox_dose_mgkg, 3)2 1.861 (0.993, 2.729) <0.0001
ns(enox_dose_mgkg, 3)3 0.955 (0.377, 1.534) 0.001
modified_cg -0.002 (-0.003, 0.000) 0.1
age 0.001 (-0.003, 0.005) 0.6

Model diagnostics

Estimated marginal means

Enoxaparin dose (mg/kg) Estimated LMWH level SE df Lower 95% CI Upper 95% CI
0.20 0.35 0.07 226 0.24 0.52
0.78 0.76 0.03 226 0.70 0.83
0.95 0.84 0.02 226 0.80 0.89
1.00 0.86 0.03 226 0.81 0.92
2.10 1.31 0.37 226 0.75 2.27

Post-hoc comparisons

NOTE: Ratio of Geometric means for every 0.1 mg/kg increase in Enoxaparin dose.

Contrast Ratio of Geometric means (95% CI) P-value
enox_dose_mgkg1 / enox_dose_mgkg0.9 1.046 (0.994, 1.100) 0.08

By dosing strategy

Model specifications
- Outcome: LMWH level
- Covariates: enoxaparin dose (mg/kg), dosing strategy, modified CrCl, age
- Model: Multiple linear regression (with non-linear terms for enoxaparin dose)
    Anti-Xa level ~ enoxaparin dose + dosing strategy + enoxaparin dose*dosing strategy+ modified CrCl + age

Global test

model term df1 df2 F.ratio p.value
enox_dose_mgkg 1 224 10.962 0.001
individualised_dose_used 1 224 2.317 0.1
modified_cg 1 224 3.116 0.08
age 1 224 0.072 0.8
(confounded) 1 224 0.002 1.0

Model summary

Var Coefficients (95% CI) P-value
(Intercept) -1.968 (-3.311, -0.625) 0.004
ns(enox_dose_mgkg, 3)1 1.748 (0.386, 3.109) 0.01
ns(enox_dose_mgkg, 3)2 4.334 (1.030, 7.637) 0.01
ns(enox_dose_mgkg, 3)3 3.003 (0.288, 5.719) 0.03
individualised_dose_usedNon-conventional 1.183 (-0.340, 2.705) 0.1
modified_cg -0.002 (-0.003, 0.000) 0.08
age 0.001 (-0.004, 0.005) 0.8
individualised_dose_usedNon-conventional:enox_dose_mgkg -1.209 (-2.769, 0.352) 0.1

Model diagnostics

Estimated marginal means

Dosing strategy Enoxaparin dose (mg/kg) Estimated LMWH level SE df Lower 95% CI Upper 95% CI
Conventional 0.20 0.13 0.09 224 0.03 0.50
Non-conventional 0.20 0.33 0.07 224 0.22 0.50
Conventional 0.78 0.61 0.10 224 0.45 0.83
Non-conventional 0.78 0.77 0.04 224 0.71 0.85
Conventional 0.95 0.80 0.04 224 0.74 0.88
Non-conventional 0.95 0.84 0.04 224 0.75 0.93
Conventional 1.00 0.87 0.03 224 0.81 0.93
Non-conventional 1.00 0.85 0.05 224 0.75 0.96
Conventional 2.10 5.16 4.97 224 0.77 34.48
Non-conventional 2.10 1.33 0.38 224 0.76 2.35

Post-hoc comparisons

Contrast Enoxaparin dose (mg/kg) Ratio of Geometric means (95% CI) P-value
(Non-conventional) / Conventional 0.2 2.56 (0.76, 8.67) 0.1
(Non-conventional) / Conventional 0.780112257281553 1.27 (0.91, 1.76) 0.2
(Non-conventional) / Conventional 0.946985771592829 1.04 (0.91, 1.19) 0.6
(Non-conventional) / Conventional 1 0.97 (0.85, 1.12) 0.7
(Non-conventional) / Conventional 2.0979020979021 0.26 (0.04, 1.52) 0.1

NOTE: Ratio of Geometric means for every 0.1 mg/kg increase in Enoxaparin dose.

Contrast individualised_dose_used Ratio of Geometric means (95% CI) P-value
enox_dose_mgkg1 / enox_dose_mgkg0.9 Conventional 1.161 (1.004, 1.344) 0.04
enox_dose_mgkg1 / enox_dose_mgkg0.9 Non-conventional 1.029 (0.966, 1.097) 0.4

Brief conclusion

Overall, dosing strategy has an effect on LMWH levels (both as a continuous measure, and whether LMWH is above range), where patients on non-conventional dose have a lower LMWH level on average.

  • [Model 1] Patients on non-conventional dose has, on average, 13% lower [Ratio of Geometic means 0.87 (95% CI 0.79 - 0.96)] in mean LMWH levels compared to those who were on conventional dose.
  • [Model 1.2] Sensitivity analysis with once-daily dosing excluded showed similar results, where patients on non-conventional dose has, on average, 16% lower [Ratio of Geometric means 0.84 (95% CI 0.76 - 0.94)] in mean LMWH levels compared to those who were on conventional dose.
  • [Model 2] There is a 54% decrease [Odds ratio 0.46 (95% CI 0.25 - 0.85)] in the risk of LMWH levels being >1.0 (vs in-range) for patients on non-conventional dose, compared to those who were on conventional dose.
  • [Model 3] There is a slight increase in the average LMWH level with increasing Enoxaparin dose. For every 10 unit increase in Enoxaparin dose, there is (on average) a 6.3% increase in the conventional dose [Ratio of Geometric means 1.063 (95% CI 1.019 - 1.108)]. Alhtough there is statsitical significance, the magnitude of effect is small and the difference may not be clinically meaningful.

Session info

Results generated on: 2023-09-12 14:58:40.381392

Click for more details

sessionInfo()
## R version 4.3.1 (2023-06-16)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 22.04.3 LTS
## 
## Matrix products: default
## BLAS:   /usr/lib/x86_64-linux-gnu/blas/libblas.so.3.10.0 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.10.0
## 
## locale:
##  [1] LC_CTYPE=en_AU.UTF-8          LC_NUMERIC=C                 
##  [3] LC_TIME=en_AU.UTF-8           LC_COLLATE=en_AU.UTF-8       
##  [5] LC_MONETARY=en_AU.UTF-8       LC_MESSAGES=en_AU.UTF-8      
##  [7] LC_PAPER=en_AU.UTF-8          LC_NAME=en_AU.UTF-8          
##  [9] LC_ADDRESS=en_AU.UTF-8        LC_TELEPHONE=en_AU.UTF-8     
## [11] LC_MEASUREMENT=en_AU.UTF-8    LC_IDENTIFICATION=en_AU.UTF-8
## 
## time zone: Australia/Adelaide
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] splines   grid      stats     graphics  grDevices utils     datasets  methods  
## [9] base     
## 
## other attached packages:
##  [1] progress_1.2.2    Hmisc_5.1-0       REDCapR_1.1.0     xlsx_0.6.5       
##  [5] DiagrammeR_1.0.10 car_3.1-2         carData_3.0-5     fontawesome_0.5.2
##  [9] MASS_7.3-60       emmeans_1.8.8     plotly_4.10.2     readxl_1.4.3     
## [13] htmlwidgets_1.6.2 kableExtra_1.3.4  knitr_1.43        ggplot2_3.4.3    
## [17] devtools_2.4.3    usethis_2.2.2     pander_0.6.5      magrittr_2.0.3   
## [21] gridExtra_2.3     rmarkdown_2.24    nvimcom_0.9-145  
## 
## loaded via a namespace (and not attached):
##  [1] remotes_2.4.2.1    sandwich_3.0-2     rlang_1.1.1        multcomp_1.4-25   
##  [5] compiler_4.3.1     systemfonts_1.0.4  callr_3.7.3        vctrs_0.6.3       
##  [9] rvest_1.0.3        stringr_1.5.0      pkgconfig_2.0.3    crayon_1.5.2      
## [13] fastmap_1.1.1      backports_1.4.1    ellipsis_0.3.2     labeling_0.4.3    
## [17] utf8_1.2.3         sessioninfo_1.2.2  ps_1.7.5           purrr_1.0.2       
## [21] xfun_0.40          cachem_1.0.8       jsonlite_1.8.7     highr_0.10        
## [25] xlsxjars_0.6.1     prettyunits_1.1.1  cluster_2.1.4      R6_2.5.1          
## [29] bslib_0.5.1        stringi_1.7.12     RColorBrewer_1.1-3 pkgload_1.3.2.1   
## [33] rpart_4.1.19       jquerylib_0.1.4    cellranger_1.1.0   estimability_1.4.1
## [37] Rcpp_1.0.11        zoo_1.8-12         base64enc_0.1-3    Matrix_1.6-1      
## [41] nnet_7.3-19        tidyselect_1.2.0   rstudioapi_0.15.0  abind_1.4-5       
## [45] yaml_2.3.7         codetools_0.2-19   processx_3.8.2     pkgbuild_1.4.2    
## [49] lattice_0.21-8     tibble_3.2.1       withr_2.5.0        coda_0.19-4       
## [53] evaluate_0.21      foreign_0.8-84     survival_3.5-7     rJava_1.0-6       
## [57] xml2_1.3.5         pillar_1.9.0       checkmate_2.2.0    generics_0.1.3    
## [61] hms_1.1.3          munsell_0.5.0      scales_1.2.1       xtable_1.8-4      
## [65] glue_1.6.2         lazyeval_0.2.2     tools_4.3.1        data.table_1.14.8 
## [69] webshot_0.5.5      fs_1.6.3           visNetwork_2.1.2   mvtnorm_1.2-3     
## [73] tidyr_1.3.0        crosstalk_1.2.0    colorspace_2.1-0   htmlTable_2.4.1   
## [77] Formula_1.2-5      cli_3.6.1          fansi_1.0.4        viridisLite_0.4.2 
## [81] svglite_2.1.1      dplyr_1.1.3        gtable_0.3.4       sass_0.4.7        
## [85] digest_0.6.33      TH.data_1.1-2      farver_2.1.1       memoise_2.0.1     
## [89] htmltools_0.5.6    lifecycle_1.0.3    httr_1.4.7